The maker of one of the SSRI market leaders is girding for a major legal battle over charges that it withheld crucial data about the drug’s efficacy and safety in children and adolescents.

Having forced an overhaul of the way the mutual fund and stock brokerage industries traditionally conduct business, New York Attorney General Eliot Spitzer has turned his sights to the pharmaceutical industry, targeting GlaxoSmithKline (GSK), one of the world’s largest drug makers.

On June 2 Spitzer filed a civil suit against GSK charging the company with fraud based on its alleged withholding of important data on clinical trials of its Paxil brand of the antidepressant paroxetine in children and adolescents.

Spitzer’s suit, filed with the Supreme Court of the State of New York, charges that GSK failed to inform physicians about clinical-trial data that raised concerns about safety and efficacy when Paxil is used to treat youngsters with depression.

GSK’s chief executive officer, Jean-Pierre Garnier, immediately denied the charges, adding that lawsuits, particularly in the United States, are “becoming an outrageous cost of doing business.” Paxil is GSK’s biggest money maker.

The U.S. Food and Drug Administration (FDA) has approved Paxil‘s use in treating depression, social anxiety disorder, generalized anxiety disorder, and obsessive-compulsive disorder in adults. Since the FDA has approved the medication, physicians can, however, prescribe it for so-called “off-label” uses, such as treating depression in children and adolescents, if they deem it to be appropriate for a particular patient. In fact, the suit notes, nearly 900,000 prescriptions for Paxil were written in 2002 to treat children and adolescents, about one-third by psychiatrists. What the FDA prohibits, though, is marketing a drug for uses not approved by the agency.

Spitzer alleges that “GSK has allowed positive information about pediatric use of paroxetine to be disclosed publicly, but has withheld and concealed negative information concerning the safety and efficacy of the drug as a treatment for pediatric MDD [major depressive disorder].”

While it conducted five trials of the antidepressant’s efficacy in children and adolescents, it published data from only one of them, he said.

By failing to disclose important clinical information to physicians, the company has prevented them “from properly and independently exercising their professional judgment on behalf of their child and adolescent patients,” according to the suit. At press time GSK has not responded to requests for comment from Psychiatric News. In a June 10 press release, the company said that its policy “is to ensure transparency of the clinical data the company collects on its marketed medicines. Specifically, we endorse the PhRMA [Pharmaceutical Research and Manufacturers of America] principles that call for timely publication of meaningful trial results.”

GSK promised to make summaries of nine studies it funded of Paxil‘s safety and efficacy in children and adolescents available on its Web site, which it did on June 14. Spitzer applauded GSK’s willingness to make these available to the public and physicians, saying that he hoped this spurs other pharmaceutical firms to follow suit.

Cover-Up Alleged

In his suit, Spitzer cites documentation produced by GSK indicating that the company planned to take steps to manage selectively any releases of data on Paxil clinical trials, so that evidence of ineffectiveness or harm was not disseminated.

He also charges that GSK “misrepresented” the drug’s efficacy in treating adolescent depression when the company briefed its sales representatives, whose job is to convince physicians to prescribe the medication. The company supplied the sales staff with a quote touting Paxil‘s “REMARKABLE efficacy and safety in the treatment of adolescent depression” when, Spitzer says, none of the studies GSK conducted on the antidepressant’s efficacy in this population demonstrated such a conclusion.

In addition, Spitzer alleges misrepresentation in the “Medical Information Letters” GSK sent to physicians about Paxil‘s effectiveness in children and adolescents with depression and failed to cite a study in which the drug turned out to be less efficacious than placebo. Through these actions, the suit charges, the company “controlled physicians’ access to negative information about paroxetine as a treatment for MDD in children and adolescents….”

The consequences of GSK’s marketing decision, the suit concludes, is that physicians were “misled and deceived” and thus unable to evaluate the prescribing information they need to provide optimal care for their patients.

Spitzer wants the court to enjoin GSK permanently from continuing the “deceptive, fraudulent, and unlawful practices alleged” in his suit and to order the company to “pay restitution and damages to all aggrieved consumers” to include “all profits from the sale of Paxil or Paxil CR in the State of New York for a child or adolescent with depressive disorder.”

Extensive Media Coverage Ensues

The suit has garnered substantial media attention in the United States and Great Britain, where GSK is headquartered. (GSK is facing a British suit over an alleged failure to tell health regulators about data pointing to a suicide risk in teenagers who are prescribed Seroxat, the brand name GSK uses for paroxetine in that country.)

A June 6 editorial in the New York Times, for example, said that “bolder action” than a lawsuit is warranted to force companies to act more responsibly. “The drug companies should be forced to make public the results of all of their clinical trials the moment they are completed, and the findings should be disseminated widely to doctors in an easy-to-understand format,” the editorial states. “Only then will patients be confident that their doctors have enough information to prescribe medicines wisely.”

A GSK press release on June 2 denies the charges, stating that the company “has acted responsibly in conducting clinical studies in pediatric patients and disseminating data from those studies. All pediatric studies have been made available to the FDA and regulatory agencies worldwide. We have publicly communicated data from all pediatric studies.”

Spitzer has indicated that GSK may not be the only pharmaceutical company at the receiving end of subpoenas from the aggressive attorney general. “This is an area we’re interested in,” he told the New York Times, “and I think there are other cases out there that are analogous.”

Barry Perlman, M.D., president of the New York State Psychiatric Association, who appeared with Spitzer in a press conference soon after the lawsuit was announced, told Psychiatric News that “we need to have a transparent system” so that doctors and patients can make fully informed decisions about treatment options. “It’s important to have drug companies make available to physicians the findings of research [the companies] subsidize, whether revealing them would be positive or adverse for their commercial interests.”

Perlman said he urged Spitzer to propose legislation in New York that would regulate such disclosure. He suggested that one strategy for such a law would be to deny inclusion on Medicaid preferred drug lists to any pharmaceutical company that declined to disclose all clinical field-trial data on one of its products.